The invention relates generally to methods of non-destructive analysis. More particularly, the invention relates to a method and device for quickly and non-destructively analyzing an array of small holes precisely placed in a material such as a thin film.
In different areas of technology it is desirable to make use of a thin sheet of material which has an array of regularly spaced, very small holes therein. For example, such might be used in the manufacture of various electronic components. Thin membranes which have one or more holes in them could also be used in the formation of components used in ink jet printers or fuel injectors. A more direct application of such a porous membrane is as a filter. The pore size and pore density could be adjusted to wide range of filter applications. Alternatively, liquid formulations containing a drug could be moved through such a porous member to create an aerosol for inhalation.
One of the gentlest and most acceptable methods of administering an agent to a patient is via aerosol. Aerosol therapy can be accomplished by aerosolization of a formulation (e.g., a drug formulation or diagnostic agent formulation) and administration to the patient, for example via inhalation. The aerosol can be used to treat lung tissue locally and/or be absorbed into the circulatory system to deliver the drug systemically. Where the formulation contains a diagnostic agent, the formulation can be used for diagnosis of, for example, conditions and diseases associated with pulmonary dysfunction.
In general, aerosolized particles for respiratory delivery must have a diameter of 12 microns or less. However, the preferred particle size varies with the site targeted (e.g, delivery targeted to the bronchi, bronchia, bronchioles, alveoli, or circulatory system). For example, topical lung treatment can be accomplished with particles having a diameter in the range of 1.0 to 12.0 microns. Effective systemic treatment requires particles having a smaller diameter, generally in the range of 0.5 to 6.0 microns, while effective ocular treatment is adequate with particles having a diameter of 15 microns or greater, generally in the range of 15-100 microns.
U.S. Pat. No. 5,544,646, 5,709,202, 5,497,763, 5,544,646, 5,718,222, 5,660,166, 5,823,178 and 5,829,435 describe devices and methods useful in the generation of aerosols suitable for drug delivery. These devices generate fine, uniform aerosols by passing a formulation through a porous membrane having micron-scale pores as may be formed, for example, by laser ablation.
Porous membranes having such small features are difficult and costly to manufacture. Additionally, the pores must be of high quality and uniformity where they are to be used (1) in manufacturing electronic components; (2) in filter materials; (3) in ink jet printers; (4) in fuel injectors; and (5) to create aerosols for delivering therapeutic agents to patients in order to insure that the patients consistently receive the therapeutically required dose. Consequently, there is a need for an inspection method which can rapidly analyze porous samples of small dimensions to determine various parameters including pore size and pore density.
Thin films having small holes therein (porous membranes) are inspected or non-destructively analyzed by (1) shining a light through the pores of the membrane (2) detecting light which has passed through the pores and (3) analyzing the detected light in a manner which makes it possible to quickly determine whether the membrane should xe2x80x9cpassxe2x80x9d inspection based on criteria such as pore size and pore density. The device used in the inspection must include (1) a light source (2) a light detector and (3) a means for analyzing the detected light. Other components may be and generally are present such as light filters and lens for improving the overall accuracy of the system and a means for moving membranes into and out of position to improve the overall efficiency of the system.
The inspection system of the invention can carry out non-destructive inspection for the presence of microscopic pores within a thin film and determine the characteristics of the porous membrane including the pore size and shape, pore density and overall acceptability of the porous membrane. The system includes the ability to detect the light transmitted through the holes within the membrane and utilize the detected light information to develop a relationship between the level of light and the size and shape of the hole, i.e. light levels detected from each hole-feature can be related to the individual size or shape of the hole. Further, the light levels from an entire array of pores within a membrane can be related to the collective average size and/or shapes of the holes. If the pores within the membrane do not meet a required criteria an alarm can be triggered at a given threshold level indicating that the porous membrane being tested does not have an adequate number of holes having the desired size and/or shape. Such an evaluation is preferably made on an overall reading of the porous membrane. More specifically, light is shown on the porous membrane and allowed to move through the holes to a detector. If a desired quantity of light is not detected by the detector there are either an insufficient number of holes or the holes are of insufficient size or some combination of both. Further, if too much light is detected than either the holes are too large or there are too many holes present in the membrane. Falling above or below the detected amount of light triggers an alarm which causes the porous membrane being inspected to be rejected.
The system is capable of being used in connection with a variety of different porous membranes. The pores can have different sizes or shapes and can be present on the membrane in a variety of different patterns and pore densities. These different membranes with different patterns and pore sizes can be detected using the same charge-coupled light detector element and processed using the same microprocessor unit. If necessary the system can utilize a variety of different components including mirrors, rhomboids, wedges, or combinations thereof in order to obtain the desired results with a given porous membrane of the same basic components of the inspection system.
The inspection system of the invention can be used to check all of the porous membranes produced by a given production system or used to spot check a certain percentage amount of those porous membranes. Further, the system can be integrated into a production system so that membranes are inspected at a given point before being used in an assembly process to produce a component which includes a porous membrane. When utilized in this manner the porous membrane need not be removed from the system for inspection purposes. Light transmitted through the pores of the membrane can be detected and used as a trigger to accept or reject the porous membrane for further use in the manufacturing process.
Porous membranes which are inspected using the present invention can be produced using focused laser light to create the pores in the membrane. The present system can utilize the light from the laser in order to carry out the inspection in real time. More specifically, the laser light used in order to create the holes can be detected by the detector and used to determine if the holes have been made, made in sufficient size and sufficient pore density. Further, the system of the invention can be used to assist in production. For example, if the laser light used in making the holes in the membrane is detected the detection of a certain amount of light can signal that the hole is sufficiently large thereby signaling that the laser light should be discontinued in order to prevent the hole from being made too large.
The present invention rapidly inspects samples for holes or through features at the micron and submicron level. This method can be used to inspect previously manufactured samples, or can be integrated into the manufacturing process in order to allow for concurrent production and inspection of samples containing such features. In one aspect of the invention, an imaging lens is used to reduce the size of the image which must be inspected, allowing for more rapid inspection and requiring a smaller CCD detector and shorter analysis time of the smaller image.
An aspect of the invention is a method of analyzing a porous membrane which involves directing light onto a porous membrane, detecting light passing through pores of the membrane and then analyzing the detected light in a manner which determines if the pores of the membrane meet desired criteria.
Another aspect of the invention is a method of analyzing a porous membrane by directing light onto the porous membrane, detecting light reflecting off of the membrane and analyzing the reflected light in a manner such that the analysis determines if pores of the membrane meet a desired criteria.
Another aspect of the invention is an analysis system which includes a means for directing light onto a porous membrane, a means for detecting light which is reflected off of and/or light which passes through pores of the membrane and a means for analyzing either the reflected light and/or the light passing through pores of the membrane so as to determine if pores of the membrane meet a desired criteria.
A preferred aspect of the invention includes a means for moving one porous membrane after another into position for analysis or moving the system relative to the membranes in order to continuously analyze one membrane after another.
In another aspect of the invention, a film, e.g. a polyimide film containing laser-ablated pores which has been inspected to determine the number and size of the pores.
In still another aspect of the invention, the light source employed produces ultraviolet light which is selectively transmitted through the features in the inspected sample.
In an additional aspect of the invention, a method of producing an aerosolization container comprising an aerosolization nozzle passing the inspection method is provided.
In a further aspect of the invention, a method of producing an aerosolization device comprising such a container is also provided.
An advantage of the invention is that porous membranes can be quickly, accurately and efficiently inspected.
A feature of the invention is that different types of light sources can be used and different types of filters can be used and positioned differently relative to the membrane being inspected.
Another feature of the invention is that the membrane may be moved relative to the light source and detector or the light source and/or detector may be moved relative to the membrane.